Anti-oxMIF Antibody Aggregation Reduction via Localized Substitutions
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Solution Overview
Problem
Current anti-oxMIF antibodies face challenges with protein aggregation and hydrophobicity, which affect their stability, manufacturing efficiency, and therapeutic efficacy, and lack enhanced effector functions necessary for effective cancer treatment.
Innovation Solution
Development of recombinant anti-oxMIF antibodies with specific amino acid substitutions in the light and heavy chain variable domains to reduce aggregation potential and hydrophobicity, while maintaining or enhancing effector functions through targeted modifications in the constant regions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If amino acid substitutions are introduced to reduce aggregation potential, then antibody stability is improved, but antibody binding affinity may be reduced
Solution Approach 1:
The patent applies local quality by introducing amino acid substitutions specifically at aggregation-prone interface regions (such as CDR-H3 and CDR-L3) while preserving the overall antibody structure and antigen-binding sites. This localized modification reduces aggregation potential without compromising global stability or binding affinity, as the substitutions are strategically placed only where aggregation occurs rather than throughout the entire antibody molecule.
Solution Approach 2:
The patent employs parameter changes by systematically varying amino acid sequences at specific positions known to be aggregation-prone. By changing parameters such as hydrophobicity, charge, and steric bulk at these critical interface regions, the patent optimizes the balance between reducing aggregation and maintaining stability, achieving reduced aggregation without sacrificing binding functionality.
2Object-affected harmful factors
If amino acid substitutions are made to reduce hydrophobicity, then solubility is improved, but protein-protein interaction strength may be reduced
Solution Approach 1:
The patent applies local quality by targeting hydrophobicity reduction specifically at surface-exposed aggregation-prone regions while preserving hydrophobic interactions at the antigen-binding interface. This localized approach reduces overall hydrophobicity and improves solubility without weakening the critical protein-protein interactions necessary for high-affinity binding to oxMIF.
Solution Approach 2:
The patent employs parameter changes by systematically modifying amino acid residues with high hydrophobicity values at aggregation-prone positions, replacing them with residues of lower hydrophobicity. This controlled parameter adjustment reduces overall protein hydrophobicity and improves solubility while maintaining the hydrophobic core interactions essential for binding strength.
3Productivity
If aggregation potential is reduced through sequence modification, then manufacturing yield is improved, but antibody efficacy may be compromised
Solution Approach 1:
The patent applies local quality by introducing modifications specifically at aggregation-prone regions identified through sequence analysis and structural modeling, rather than throughout the entire antibody. This localized approach improves manufacturing yield by reducing aggregate formation during production while preserving the efficacy-critical regions responsible for oxMIF binding and biological activity.
Solution Approach 2:
The patent employs preliminary action by identifying and modifying aggregation-prone regions through in silico analysis and structural modeling before actual antibody production. This preliminary sequence optimization prevents aggregation issues from arising during manufacturing, improving yield while ensuring the modified antibody maintains full efficacy through validated binding assays.
Data Source
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AI summary
The invention refers to anti-oxMIF antibodies with improved properties such as reduced aggregation potential and reduced hydrophobicity due to selected amino acid substitutions in the light and heavy chain variable domains and optionally increased effector functions due to further substitutions in the heavy chain constant regions, and their use in the treatment of oxMIF-related conditions.